The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth

Gastrointestinal stromal tumors (GISTs) are the most common neoplasms of mesenchymal origin, and most of them emerge due to the oncogenic activation of KIT or PDGFRA receptors. Despite their relevance in GIST oncogenesis, critical intermediates mediating the KIT/PDGFRA transforming program remain mo...

ver descrição completa

Detalhes bibliográficos
Autores: Proaño Pérez, Elizabeth, Serrano Candelas, Eva, 1982-, García-Valverde, Alfonso, Rosell, Jordi, Gómez Peregrina, David, Navinés Ferrer, Arnau, Guerrero, Mario, Serrano, César, Martín Andorrà, Margarita
Tipo de documento: artigo
Data de publicação:2022
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/207000
Acesso em linha:https://hdl.handle.net/2445/207000
http://doi.org/10.1038/s41417-022-00539-1
Access Level:Acceso aberto
Palavra-chave:Factors de transcripció
Càncer gastrointestinal
Cèl·lules
Apoptosi
Transducció de senyal cel·lular
Transcription factors
Gastrointestinal cancer
Cells
Apoptosis
Cellular signal transduction
id ES_e2ec7273f7757d97e05fe8bf1c39b839
oai_identifier_str oai:diposit.ub.edu:2445/207000
network_acronym_str ES
network_name_str España
repository_id_str
spelling The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growthProaño Pérez, ElizabethSerrano Candelas, Eva, 1982-García-Valverde, AlfonsoRosell, JordiGómez Peregrina, DavidNavinés Ferrer, ArnauGuerrero, MarioSerrano, CésarMartín Andorrà, MargaritaFactors de transcripcióCàncer gastrointestinalCèl·lulesApoptosiTransducció de senyal cel·lularTranscription factorsGastrointestinal cancerCellsApoptosisCellular signal transductionGastrointestinal stromal tumors (GISTs) are the most common neoplasms of mesenchymal origin, and most of them emerge due to the oncogenic activation of KIT or PDGFRA receptors. Despite their relevance in GIST oncogenesis, critical intermediates mediating the KIT/PDGFRA transforming program remain mostly unknown. Previously, we found that the adaptor molecule SH3BP2 was involved in GIST cell survival, likely due to the co-regulation of the expression of KIT and Microphthalmia-associated transcription factor (MITF). Remarkably, MITF reconstitution restored KIT expression levels in SH3BP2 silenced cells and restored cell viability. This study aimed to analyze MITF as a novel driver of KIT transforming program in GIST. Firstly, MITF isoforms were characterized in GIST cell lines and GIST patients' samples. MITF silencing decreases cell viability and increases apoptosis in GIST cell lines irrespective of the type of KIT primary or secondary mutation. Additionally, MITF silencing leads to cell cycle arrest and impaired tumor growth in vivo. Interestingly, MITF silencing also affects ETV1 expression, a linage survival factor in GIST that promotes tumorigenesis and is directly regulated by KIT signaling. Altogether, these results point to MITF as a key target of KIT/PDGFRA oncogenic signaling for GIST survival and tumor growth.Springer Nature2022info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2445/207000http://doi.org/10.1038/s41417-022-00539-1Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a http://doi.org/10.1038/s41417-022-00539-1Cancer Gene Therapy, 2022, vol. 30, num.2, p. 245-255(c) Proaño Pérez, Elizabeth et al., 2022info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2070002026-05-27T06:46:51Z
dc.title.none.fl_str_mv The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
title The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
spellingShingle The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
Proaño Pérez, Elizabeth
Factors de transcripció
Càncer gastrointestinal
Cèl·lules
Apoptosi
Transducció de senyal cel·lular
Transcription factors
Gastrointestinal cancer
Cells
Apoptosis
Cellular signal transduction
title_short The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
title_full The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
title_fullStr The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
title_full_unstemmed The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
title_sort The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
dc.creator.none.fl_str_mv Proaño Pérez, Elizabeth
Serrano Candelas, Eva, 1982-
García-Valverde, Alfonso
Rosell, Jordi
Gómez Peregrina, David
Navinés Ferrer, Arnau
Guerrero, Mario
Serrano, César
Martín Andorrà, Margarita
author Proaño Pérez, Elizabeth
author_facet Proaño Pérez, Elizabeth
Serrano Candelas, Eva, 1982-
García-Valverde, Alfonso
Rosell, Jordi
Gómez Peregrina, David
Navinés Ferrer, Arnau
Guerrero, Mario
Serrano, César
Martín Andorrà, Margarita
author_role author
author2 Serrano Candelas, Eva, 1982-
García-Valverde, Alfonso
Rosell, Jordi
Gómez Peregrina, David
Navinés Ferrer, Arnau
Guerrero, Mario
Serrano, César
Martín Andorrà, Margarita
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Factors de transcripció
Càncer gastrointestinal
Cèl·lules
Apoptosi
Transducció de senyal cel·lular
Transcription factors
Gastrointestinal cancer
Cells
Apoptosis
Cellular signal transduction
topic Factors de transcripció
Càncer gastrointestinal
Cèl·lules
Apoptosi
Transducció de senyal cel·lular
Transcription factors
Gastrointestinal cancer
Cells
Apoptosis
Cellular signal transduction
description Gastrointestinal stromal tumors (GISTs) are the most common neoplasms of mesenchymal origin, and most of them emerge due to the oncogenic activation of KIT or PDGFRA receptors. Despite their relevance in GIST oncogenesis, critical intermediates mediating the KIT/PDGFRA transforming program remain mostly unknown. Previously, we found that the adaptor molecule SH3BP2 was involved in GIST cell survival, likely due to the co-regulation of the expression of KIT and Microphthalmia-associated transcription factor (MITF). Remarkably, MITF reconstitution restored KIT expression levels in SH3BP2 silenced cells and restored cell viability. This study aimed to analyze MITF as a novel driver of KIT transforming program in GIST. Firstly, MITF isoforms were characterized in GIST cell lines and GIST patients' samples. MITF silencing decreases cell viability and increases apoptosis in GIST cell lines irrespective of the type of KIT primary or secondary mutation. Additionally, MITF silencing leads to cell cycle arrest and impaired tumor growth in vivo. Interestingly, MITF silencing also affects ETV1 expression, a linage survival factor in GIST that promotes tumorigenesis and is directly regulated by KIT signaling. Altogether, these results point to MITF as a key target of KIT/PDGFRA oncogenic signaling for GIST survival and tumor growth.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/207000
http://doi.org/10.1038/s41417-022-00539-1
url https://hdl.handle.net/2445/207000
http://doi.org/10.1038/s41417-022-00539-1
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a http://doi.org/10.1038/s41417-022-00539-1
Cancer Gene Therapy, 2022, vol. 30, num.2, p. 245-255
dc.rights.none.fl_str_mv (c) Proaño Pérez, Elizabeth et al., 2022
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Proaño Pérez, Elizabeth et al., 2022
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422454729867264
score 15,301603

Registros relacionados